Maintenance rTMS for Depression (Maitr-De) (Maitr-De)

April 23, 2026 updated by: Zafiris Daskalakis, University of California, San Diego

Maintaining the Acute Therapeutic Effect of rTMS in Treatment-Resistant Depression (Maitr-De)

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for treatment-resistant depression (TRD), yet substantial uncertainties persist regarding its efficacy as a maintenance treatment. This prospective study seeks to investigate the efficacy of maintenance rTMS in individuals with TRD who have previously responded to an acute course of rTMS. In the R61 phase of the study, we will recruit 75 participants across three study sites, the University of California San Diego, Weill Cornell Medicine, and Australian National University, into a double-blind, three-arm maintenance treatment trial. In this trial, participants will be randomized to receive either standard maintenance rTMS, clustered maintenance rTMS, or sham maintenance rTMS for a duration of 6 months. Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period. We will also assess changes in depressive symptom severity using clinical scales, including the Montgomery-Asberg Depression Rating Scale (MADRS) as a secondary outcome measure. It is hypothesized that stimulation with clustered maintenance rTMS will demonstrate superiority in sustaining DLPFC-SGC connectivity compared with standard maintenance rTMS and sham maintenance rTMS

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Australia, 2601
        • Recruiting
        • Australian National University
        • Contact:
        • Principal Investigator:
          • Paul B Fitzgerald, MPM, PhD
  • United States
    • California
      • San Diego, California, United States, 92127
        • Recruiting
        • University of California, San Diego
        • Contact:
        • Principal Investigator:
          • Zafiris J Daskalakis, MD. Ph.D.
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell Medicine
        • Contact:
        • Principal Investigator:
          • Conor M Liston, PhD, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. They met criteria for a DSM-5 diagnosis of a Major Depressive Episode (MDE) during the index episode of depression for which they have received an acute rTMS treatment course.
  2. Meet criteria for either response or remission from their initial depressive illness. The MINI assessment timeline will be adjusted to allow scoring of illness symptoms prior to rTMS response. Response to acute course of treatment is defined as either a MADRS score of <10, or a MADRS score of 10-19, plus evidence of having met response criteria on either the MADRS or another structured depression rating scale. The response is defined as a >50% reduction in the total score from the start to the end of treatment.
  3. Their initial rTMS treatment course must have consisted of at least 15 rTMS treatment sessions.
  4. People between the ages of 18 and 80 at the time of screening. A written statement from the referring physician will be required to confirm that the participant demonstrates the capacity to consent.
  5. Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during TMS-EEG assessments and iTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
  6. In good general health, as evidenced by medical history.
  7. Agreement to adhere to Lifestyle Considerations throughout study duration.
  8. If a person of child-bearing potential is: must take a pregnancy test at the screening visit, with results confirmed as negative by study staff

Exclusion Criteria:

  • 1. Pregnancy 2. History of or current psychotic disorder or depression with psychotic features 3. Severe borderline personality disorder based on clinical assessment. 4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder 5. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal 6. Clinically significant suicidal ideation with plan 7. Any history of ECT (greater than 8 sessions) without a clinical meaningful response in the current episode.

    8. Recent (during the current depressive episode) or concurrent use of rapid-acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days 9. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma 10. Untreated or insufficiently treated endocrine disorder. 11. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) 12. Treatment with an investigational drug or other intervention within the study period 13. The patient experiences a relapse between baseline and screening, defined as a moderate depression (MADRS >=20) and a 25% increase from screening to baseline 14. Require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any anticonvulsant (with the exception of Gabapentin, pregabalin, and lamotrigine).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clustered maintenance rTMS
Clustered maintenance treatment involves administering four sessions of rTMS over a two-day span, conducted once per month for six months.
Device: Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:
Clustered maintenance rTMS typically involves around 4 TMS sessions applied over 2 days, at 1-month intervals. Our team initially developed this approach based upon preclinical TMS studies (for example (Maeda et al. 2000)) suggesting that rTMS treatment effects may accumulate when applied over multiple sessions in a shorter period of time (Maeda et al. 2000).
Active Comparator: Standard maintenance rTMS:
Standard maintenance rTMS involves a course of rTMS with once-weekly sessions for 6 months.
Device: Transcranial Magnetic Stimulation (TMS) - Standard maintenance rTMS:
In this approach, patients who were treated with rTMS five days per week during their acute episode receive less frequent treatments during a taper period (for example treatment three days per week followed by two sessions per week) with a gradual transition into a maintenance schedule. For example, the maintenance schedule might begin with a single weekly session for one or two months and then the intensity is reduced to one session every two weeks (and possibly then one session every three or four weeks).
Placebo Comparator: sham maintenance rTMS
Somatosensory-matched placebo rTMS is delivered according to either standard or clustered maintenance schedules over a six-month period (50/50% allotment). Patient's maintenance protocol parameters will otherwise mirror those used during their acute treatment with identical cortical targets, stimulation intensity, frequency, and duration. Sham TMS-EEG will be conducted by rotating the coil 90 degrees while maintaining contact with the scalp. This standard practice prevents current induction while replicating the auditory click associated with TMS, ensuring comparable EEG recordings
Device: Transcranial Magnetic Stimulation (TMS) -- Sham maintenance rTMS
Sham treatment will be administered as either standard or clustered maintenance rTMS for 6 months period using a sham coil. The intervention target will be located via a Brainsight TMS Navigator (Brainsight, Montreal, Canada). For safety reasons, the individual TMS intensity will be limited to 130% of the individual resting motor threshold.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aim: To evaluate the effects of two active rTMS maintenance treatments (i.e., standard and clustered) compared to sham maintenance rTMS on DLPFC-SGC connectivity.
Time Frame: 6-months
Our primary aim is to examine the efficacy of maintenance rTMS on sustaining connectivity between the dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate cortex (SGC) measured through concurrent TMS and electroencephalography (TMS-EEG) at baseline and every six weeks throughout the 6-month treatment period
6-months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

National Institute of Mental Health (NIMH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2025

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

April 14, 2025

First Submitted That Met QC Criteria

April 14, 2025

First Posted (Actual)

April 22, 2025

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 811708

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Major Depressive Disorder

Clinical Trials on Transcranial Magnetic Stimulation (TMS) - Clustered maintenance rTMS:

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gabon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe